Procedures and Patients

The procedures used in this study conformed to the tenets of the Declaration of Helsinki. Treatment of an intravitreal injection of bevacizumab was approved by the Institutional Review Board for Nara Medical University. An informed consent was obtained from all of the patients after an explanation of the procedures to be used and possible complications.

We studied the medical records of patients with a resolved macular edema associated with BRVO and with an intact IS/OS line at the central fovea in the SDOCT images. All of the patients were examined at the Nara Medical University Hospital from June 1, 2011 to April 30, 2013. Eyes with coexisting ocular diseases (eg, epiretinal membrane, glaucoma, diabetic retinopathy, vitreous hemorrhage, vitreous opacity, and senile cataract) were excluded. In the end, 31 eyes of 31 patients with macular edema associated with BRVO (BRVO group) were studied. We also studied the 31 unaffected fellow eyes as controls (control group). Twenty-seven of the 31 affected eyes received an intravitreal injection of bevacizumab and a posterior sub-Tenon injection of triamcinolone acetonide to treat the macular edema. The macular edema resolved spontaneously in the other 4 eyes. All of the patients underwent a complete ophthalmic examination including the measurement of the best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination including slit-lamp biomicroscopy with a noncontact fundus lens, fundus photography, and SDOCT.

Evaluation of Optical Coherence Tomographic Images

The Spectralis SDOCT (Heidelberg Engineering, Heidelberg, Germany) was used to obtain the SDOCT images. We evaluated the horizontal cross-sectional images that were recorded at the initial and final visit after resolution of the macular edema. The central foveal thickness (CFT) was measured as the distance between the internal limiting membrane (ILM) and the outer border of the retinal pigment epithelium (RPE) at the central fovea. The CFT was measured automatically with the caliper measurement tool embedded in the SDOCT system ( Figure 1 ). We also measured the outer nuclear layer (ONL) thickness as the distance between the outer border of the ILM and the external limiting membrane (ELM), and the photoreceptor inner segment (IS) length as the distance between the ELM and the inner border of the highly reflective line representing the IS/OS line at the central fovea. The photoreceptor outer segment (OS) length was measured as the distance between the IS/OS line and the inner border of the RPE at the center of the fovea ( Figure 1 ). The ONL thickness and the photoreceptor IS and OS lengths were measured manually by 2 of the authors (T.H. and M.O.), who were masked to the visual acuity and other information of the eyes. The values obtained by the 2 authors were averaged for the statistical analyses. The intraclass correlation coefficient (ICC) was calculated as an interobserver reproducibility measure.

Spectral-domain optical coherence tomography (SDOCT) image of a normal eye of a 53-year-old woman whose decimal best-corrected visual acuity was 1.2. (Top) Horizontal scan across the central fovea that was obtained at a 30-degree angle. SDOCT image shows that the photoreceptor inner segment/outer segment (IS/OS) line has a bulge at the central fovea, named a foveal bulge (arrow). (Bottom) Magnified view. The central foveal thickness (CFT) is the distance between the surface of the internal limiting membrane (ILM) and the outer border of the retinal pigment epithelium (RPE) at the central fovea. The thickness of the outer nuclear layer (ONL) is the distance between the outer border of the ILM and the external limiting membrane (ELM). The length of the photoreceptor inner segment (IS) is the distance between the ELM and the inner border of the IS/OS line. The length of the photoreceptor outer segment (OS) is the distance between the inner border of the IS/OS and the inner border of the RPE.

We focused on the foveal bulge as seen in normal eyes ( Figure 1 ) in the 31 BRVO eyes of 31 patients. The eyes were classified into those with a foveal bulge and those without a foveal bulge. The same retinal specialists (T.H. and M.O.) evaluated the foveal shape in the OCT images and were masked to the clinical characteristics of the eyes, and a third reviewer (T.U.), who was also masked to the patients’ data, made the final decision regarding the presence or absence of a foveal bulge in cases of disagreement.

Statistical Analyses

Statistical analyses were performed using StatView software (version 5.0; SAS Institute, Cary, North Carolina, USA). The BCVA was measured with a Landolt chart, and the decimal acuities were converted to the logarithm of the minimal angle of resolution (logMAR) for the statistical analyses. All values are presented as the means ± standard deviations. The Mann-Whitney U test was used to determine the significance of differences in the patient characteristics and the retinal thicknesses. The significance of the differences in the incidence of an intact the ELM, presence of serous retinal detachment (SRD), and foveal bulge was analyzed with the Fisher exact probability test. A P value <.05 was considered statistically significant.

Comparisons Between Control Group and Branch Retinal Vein Occlusion Group

The clinical characteristics of the eyes in the BRVO group and control fellow eyes at the final visit are summarized in Table 1 . In the BRVO group, the mean BCVA was 0.18 ± 0.22 logMAR units with a range of −0.08 to 0.52 logMAR units, the mean CFT was 221.8 ± 20.5 μm, and the mean photoreceptor OS length at the central fovea was 47.3 ± 9.4 μm. For the eyes in the control group, the mean BCVA was −0.03 ± 0.05 logMAR units, the mean CFT was 221.2 ± 15.9 μm, and the mean photoreceptor OS length was 58.5 ± 4.2 μm. The BCVA in eyes of the control group was significantly better than that in eyes of the BRVO group ( P < .0001). The photoreceptor OS length in eyes of the BRVO group was significantly shorter than that in eyes of the control group ( P < .0001), but the CFT, ONL thickness, and photoreceptor IS length were not significantly different between the eyes of the 2 groups.

In the control group, a foveal bulge was present in all 31 eyes (100%) at the final visit, but a foveal bulge was present in 7 eyes (22.6%) and absent in 24 (77.4%) in the BRVO group at the final visit. This difference in the incidence of a foveal bulge at the final visit was significant ( P < .0001).

Comparisons of Eyes With or Without Foveal Bulge in Branch Retinal Vein Occlusion Group

At the final visit, a foveal bulge was present in 7 and not present in 24 eyes of the BRVO group. The clinical characteristics of the eyes in the foveal bulge (+) group (n = 7) and foveal bulge (−) group (n = 24) are presented in Table 2 . At the final visit in the foveal bulge (+) group, the mean BCVA was −0.06 ± 0.04 logMAR units, the mean CFT was 237.0 ± 17.7 μm, and the mean photoreceptor OS length at the central fovea was 58.6 ± 3.8 μm. In the foveal bulge (−) group, the mean BCVA was 0.24 ± 0.21 logMAR units, the mean CFT was 217.3 ± 19.3 μm, and the mean photoreceptor OS length was 44.0 ± 7.8 μm at the final visit. At the final visit, the BCVA was significantly better in the foveal bulge (+) group than in the foveal bulge (−) group ( P < .0001). The CFT was significantly thicker and the photoreceptor OS length was significantly longer in the foveal bulge (+) group than in the foveal bulge (−) group ( P = .0248, P = .0001, respectively). On the other hand, the ONL thickness and photoreceptor IS length were not significantly different in the 2 groups.

We also studied the differences in the age, BCVA, and OCT findings at the initial examination between the foveal bulge (+) group and the foveal bulge (−) group. The patients in the foveal bulge (+) group were significantly younger than those in the foveal bulge (−) group ( P = .044). The BCVA was significantly better and the CFT was significantly thinner in the foveal bulge (+) group than that in the foveal bulge (−) group ( P = .0034, P = .0011, respectively). At the initial visit, a disrupted ELM was present in 1 of 7 eyes (14.3%) in the foveal bulge (+) group but was disrupted in 17 of 24 eyes (70.8%) in the foveal bulge (−) group. In addition, an SRD was detected beneath the fovea in only 1 of 7 eyes (14.3%) in the foveal bulge (+) group, but in 20 of 24 eyes (83.3%) in the foveal bulge (−) group. The incidence of a disrupted ELM in the foveal bulge (+) group was significantly lower than that in the foveal bulge (−) group ( P = .0124), and the incidence of an SRD in the foveal bulge (+) group was also significantly lower than that in the foveal bulge (−) group ( P = .0017). At the initial visit, the foveal bulge could be detected in 6 of 7 eyes (85.7%) in the foveal bulge (+) group, but the foveal bulge could be detected in only 1 of the 24 eyes (4.2%) in the foveal bulge (−) group ( P < .0001).

Correlations Between Clinical Characteristics and Final Visual Acuity

We classified 31 BRVO eyes into eyes with a decimal BCVA of ≥1.0 (n = 9) and eyes with a decimal BCVA of <1.0 (n = 22; Table 3 ). Seven of 9 eyes (77.8%) with a decimal BCVA of ≥1.0 had a foveal bulge after resolution of the macular edema. In eyes with a decimal BCVA of <1.0, none had a foveal bulge. This difference in the number of eyes with a foveal bulge after resolution of the macular edema was significant ( P < .0001). Furthermore, the initial clinical characteristics (eg, age, BCVA, CFT, integrity of the ELM, SRD, and foveal bulge) were significantly different in the eyes with a decimal BCVA of ≥1.0 and the eyes with BCVA of <1.0.

Table 3

Comparison of Eyes With or Without Decimal Best-Corrected Visual Acuity of ≥1.0 After Resolution of Macular Edema Associated With Branch Retinal Vein Occlusion

	Decimal BCVA of ≥1.0 (n = 9)	Decimal BCVA of <1.0 (n = 22)	P Value
Age (y)	59.8 ± 10.6	70.4 ± 5.2	.0088
Follow-up period (mo)	7.9 ± 4.8	7.3 ± 4.1	.8780
Initial examination
LogMAR	0.14 ± 0.14	0.48 ± 0.27	.0005
CFT (μm)	343.0 ± 167.8	566.3 ± 155.9	.0017
Disrupted ELM n (%)	2 (22.2%)	16 (72.7%)	.0166
Detection of SRD n (%)	2 (22.2%)	19 (86.4%)	.0013
Detection of foveal bulge n (%)	6 (66.7%)	1 (4.5%)	.0007
Final examination
LogMAR	−0.04 ± 0.04	0.27 ± 0.21	<.0001
CFT (μm)	232.9 ± 18.0	217.2 ± 20.0	.0476
ONL thickness (μm)	109.3 ± 9.6	105.1 ± 12.6	.5136
Photoreceptor IS length (μm)	28.5 ± 1.5	28.0 ± 1.6	.4558
Photoreceptor OS length (μm)	56.6 ± 6.1	43.5 ± 7.6	.0002
Detection of foveal bulge n (%)	7 (77.8%)	0 (0%)	<.0001

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